Study design, setting, and participants
This was a retrospective case control-study, conducted in a university-affiliated medical center (Cathay General Hospital, Taipei) in Northern Taiwan; there were 40 ED beds and 800 ward beds, with approximately 55,000 visiting patients annually. The study period was between January 01, 2014 and December 31, 2017. Patients who fulfilled the following inclusion criteria were included: (1) aged above 18 years, (2) suspected of bacterial infection, and (3) positive bacterial culture obtained from blood or sputum or urine obtained in the ED. Patients who were transferred from other hospitals, had out-of-hospital cardiac arrest, were pregnant, or had mixed infections were excluded.
Definition of variables and primary outcome
Suspected bacterial infection is identified by: (1) physician’s clinical judgment through chart review and infection related disease codes, or (2) ED clinical parameters that indicate infection, such as severe inflammatory response syndrome (SIRS) and quick sepsis-related organ failure assessment (qSOFA) score. SIRS is defined as a heart rate > 90 beats per minute, respiratory rate > 20 breaths per minute, temperature < 36°C or > 38°C, white blood cell count < 4000 / mm3 or > 12 000 / mm3, and band form > 10% [10]. qSOFA score is defined as systolic blood pressure ≤ 100 mmHg, respiratory rate ≥ 22 breaths per minute, and Glasgow Coma Scale < 15 [11]. Two sets of blood cultures, all together four bottles (two aerobic bottles, two anaerobic bottles), were collected from each patient via peripheral venipuncture at two different sites, with a 30-minute interval between sample collections. Positive blood culture is defined as at least two bottles of blood culture yielding the same pathogen [12]. Positive sputum culture is defined as pathogen growth in sputum specimens with fewer than 25 squamous epithelial cells per low-power field [13]. Positive urine culture is defined as pathogen growth > 105 colony-forming unit (CFU) per milliliter in clean-catch midstream urine specimens [14].
Data collection and assignment to case and control groups
The retrospective chart review method was used to acquire data of patients who fulfilled the inclusion criteria. Demographic characteristics, including vital signs (obtained at the ED triage), laboratory data, infection sites, cultured microorganisms, qSOFA scores, SIRS criteria, and clinical outcomes, were obtained by an emergency physician (Table 1). In total, 903 bacteria-infected ED patients were initially recruited, with a total of 797 patients included in the study. Exclusions (106 patients) were made for insufficient data, presence of mixed infections, occurrence of an out-of-hospital cardiac arrest, transferal of patients treated at other hospitals, or pregnant patients (Figure 1). The recruited patients were further divided into two groups based on the culture result, with 278 patients assigned to the GNB group and 519 patients to the non-GNB group. All variables were compared between the two groups, and the accuracy of clinical parameters to predict GNB infection were also analyzed.
Ethical statement
This study was approved by the institutional Review Board of the Cathay General Hospital and was conducted according to the Declaration of Helsinki. This was an observational study; the need for informed consent from the patients was not necessary.
Statistical analysis
We used SPSS 23.0 for Mac (SPSS Inc., Chicago, IL, USA) to perform statistical analysis. Continuous data were presented as mean ± standard deviation (SD), while categorical variables were presented as percentages. Independent samples t-test, the Mann–Whitney, or Wilcoxon test were used to analyze continuous variables. Pearson’s chi-square test or Fisher’s exact test was used for categorical variables. Logistic regression was performed to evaluate the prediction of GNB infection among the four clinical parameters that showed significant difference (p < 0.05) between the GNB and the non-GNB group (Table 2). The optimal cut-off point of each clinical parameter used to predict GNB infection was calculated via Youden index. The area under the receiver operating characteristic curve (AUROC) was then used to evaluate GNB prediction discrimination ability (Table 3).